Pesticidal n-heteroaryl alpha-alkoximino-carboxamides

ABSTRACT

The invention relates to compounds of the general formula                    
     wherein R 1  is hydrogen, halogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkyl or unsubstituted or mono- to penta-substituted phenyl, whereby the substituents are selected from the group comprising C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, aryloxy, halogen, cyano and nitro, whereby if the number of substituents is greater than 1, the substituents may be identical or different; R 2  is hydrogen, C 1 -C 6 -alkyl, (C 1 -C 6 -alkylene)phenyl, pyridyl, COOR 6 , CONR 7 R 8 COR 6 , allyl or CH 2 —O—R 6 ; R 3  is C 1 -C 6 -alkyl; R 4  is unsubstituted or substituted phenyl, unsubstituted or substituted benzyl or unsubstituted or substituted heterocyclyl, whereby each of the substituents, independently of each other, is selected from the group comprising C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, aryloxy, halogen, cyano, hydroxy, amino and nitro, whereby if the number of substituents is greater than 1, the substituents may be identical or different; R 6  is C 1 -C 6 -alkyl, phenyl or benzyl; R 7  and R 8  independently of one another, are hydrogen or C 1 -C 6 -alkyl; Q is C 1 -C 6 -alkylene; X 1  is N or C(CN); X 2  is N, C(CN), C(COOR 6 ), C(COR 6 ), C(SOR 6 ), C(CONR 7 R 8 ) or C(NO 2 ); X 3  and X4, independently of each other, are O or S; and n is 0 or 1 and optionally the enantiomers thereof. The active ingredients have advantageous pesticidal properties. They are especially suitable for the control of pests on domestic animals and livestock.

This application is a 371 of PCT/EP00/11840 filed on Nov. 27, 2000.

The present invention relates to new substituted aminoheterocyclylamidesof formula

wherein

R₁ is hydrogen, halogen, C₁-C₆-alkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkyl orunsubstituted or mono- to penta-substituted phenyl, whereby thesubstituents are selected from the group comprising C₁-C₆-alkyl,C₁-C₆-haloalkyl, C₁-C₆-alkoxy, aryloxy, halogen, cyano and nitro,whereby if the number of substituents is greater than 1, thesubstituents may be identical or different;

R₂ is hydrogen, C₁-C₆-alkyl, (C₁-C₆-alkylene)phenyl, pyridyl, COOR₆,CONR₇R₈, COR₆, allyl or CH₂—O—R₆;

R₃ is C₁-C₆-alkyl;

R₄ is unsubstituted or substituted phenyl, unsubstituted or substitutedbenzyl or unsubstituted or substituted heterocyclyl, whereby each of thesubstituents, independently of each other, is selected from the groupcomprising C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, aryloxy, halogen,cyano, hydroxy, amino and nitro, whereby if the number of substituentsis greater than 1, the substituents may be identical or different.

R₆ is C₁-C₆-alkyl, phenyl or benzyl;

R₇ and R₈ independently of one another, are hydrogen or C₁-C₆-alkyl;

Q is C₁-C₆-alkylene;

X₁ is N or C(CN);

X₂ is N, C(CN), C(COOR₆), C(COR₆), C(SOR₆), C(CONR₇R₈) or C(NO₂);

X₃ and X₄, independently of each other, are O or S; and

n is 0 or 1;

the preparation thereof and the use thereof in the control of pests, andalso pesticides containing at least one of these compounds.

Substituted aminoheterocyclylamides having pesticidal activity aredescribed for example in DE 197 27 162. However, the active ingredientsspecifically disclosed therein cannot always fulfil the requirementsregarding potency and activity spectrum. There is therefore a need foractive ingredients with improved pesticidal properties. It has now beenfound that the aminoheterocyclylamides of formula I have excellentpesticidal properties, especially against endoparasites.

The alkyl groups present in the definitions of the substituents may bestraight-chained or branched and are for example methyl, ethyl,n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, pentyland hexyl, as well as the branched isomers thereof.

Corresponding alkylene groups may likewise be straight-chained orbranched and are for example methylene, ethylene, n-propylene,isopropylene, n-butylene, sec.-butylene, isobutylene, tert.-butylene,pentylene and hexylene, as well as the branched isomers thereof.

As a rule, halogen signifies fluorine, chlorine, bromine or iodine. Thesame applies to halogen in combination with other significances, such ashalogenalkyl or halogenphenyl.

Halogenalkyl groups preferably have a chain length of 1 to 6 carbonatoms. Halogenalkyl is for example fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl,1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and2,2,2-trichloroethyl; preferably trichloromethyl, difluorochloromethyl,difluoromethyl, trifluoromethyl and dichlorofluoromethyl.

Alkoxy groups preferably have a chain length of 1 to 6 carbon atoms.Alkoxy is for example methoxy, ethoxy, propoxy, isopropoxy, n-butoxy,isobutoxy, sec.-butoxy and tert.-butoxy, as well as the isomerspentyloxy and hexyloxy; preferably methoxy and ethoxy.

Heterocyclyl signifies an aliphatic or aromatic, optionallybenzocondensed, threefold to eightfold, cyclic group which contains atleast one hetero atom from the group comprising oxygen, nitrogen andsulphur, with five- and sixfold heterocycles being preferred. Typicalrepresentatives are, for example, dioxolanyl, pyrrolidinyl, piperidinyl,morpholinyl, pyridyl, pyrryl, furyl, thienyl, imidazolyl,tetrahydrofuryl, tetrahydropyrryl, tetrahydropyranyl, dihydrofuryl,dihydropyranyl, benzofuryl, benzothienyl, isoxazolyl, oxazolyl,thiazolyl, oxazolinyl, oxazolidinyl, indolyl, imidazolinyl,imidazolidinyl and dioxanyl.

Preferred compounds within the context of formula I are those in which

R₁ is halogen, C₁-C₆-alkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkyl orunsubstituted or mono- to penta-substituted phenyl, whereby thesubstituents are selected from the group comprising

C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, aryloxy, halogen, cyano andnitro, whereby if the number of substituents is greater than 1, thesubstituents may be the same or different;

R₂ is hydrogen, C₁-C₆-alkyl, (C₁-C₆-alkylene)phenyl or pyridyl;

R₃ is C₁-C₆-alkyl;

R₄ is unsubstituted or substituted phenyl, unsubstituted or substitutedbenzyl or unsubstituted or substituted heterocyclyl, whereby each of thesubstituents, independently of each other, is selected from the groupcomprising C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, aryloxy, halogen,cyano, hydroxy, amino and nitro, whereby if the number of substituentsis greater than 1, the substituents may be identical or different.

Q is C₁-C₆-alkylene;

X₁ is N or C(CN);

X₂ is N or C(CN);

X₃ and X₄, independently of each other, are O or S; and

n is 0 or 1.

Especially preferred embodiments in the context of the compounds offormula I are:

(1) A compound of formula I, wherein R₁ is halogen or C₁-C₆-haloalkyl;preferably fluorine, chlorine or C₁-C₄-haloalkyl; more preferablychlorine or C₁-C₂-haloalkyl; most preferably chlorine ortrifluoromethyl;

(2) A compound of formula I, wherein R₂ is hydrogen or C₁-C₆-alkyl;preferably hydrogen or C₁-C₂-alkyl; most preferably hydrogen;

(3) A compound of formula I, wherein R₃ is C₁-C₄-alkyl; preferablyC₁-C₂-alkyl; most preferably methyl;

(4) A compound of formula I, wherein R₄ is unsubstituted or substitutedheterocyclyl, whereby the substituents are selected from the groupcomprising C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, aryloxy, halogen,cyano, hydroxy, amino and nitro, whereby if the number of substituentsis greater than 1, the substituents may be identical or different;preferably unsubstituted or substituted heterocyclyl, whereby thesubstituents are selected from the group comprising halogen, cyano andnitro, whereby if the number of substituents is greater than 1, thesubstituents may be identical or different; more preferablyunsubstituted or substituted heterocyclyl, whereby the substituents areselected from the group comprising fluorine, chlorine or bromine,whereby if the number of substituents is greater than 1, thesubstituents may be identical or different; most preferablyunsubstituted or chlorine-substituted heterocycly; especiallypyrrolidinyl, piperidinyl, pyridyl, pyrryl, furyl, thienyl,tetrahydrofuryl, benzofuryl or benzothienyl;

(5) A compound of formula I, wherein Q is C₁-C₂-alkylene;

(6) A compound of formula I, wherein X₃ is O;

(7) A compound of formula I, wherein X₄ is O;

(8) A compound of formula I, wherein n is 1;

(9) A compound of formula I, wherein R₁ is halogen or C₁-C₆-haloalkyl;R₂ is hydrogen or C₁-C₆-alkyl; R₃ is C₁-C₄-alkyl; R₄ is unsubstituted orsubstituted heterocyclyl, whereby the substituents are selected from thegroup comprising C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, aryloxy,halogen, cyano, hydroxy, amino and nitro, whereby if the number ofsubstituents is greater than 1, the substituents may be identical ordifferent; Q is C₁-C₂-alkylene; X₃ and X₄ are O; and n is 1;

(10) A compound of formula I, wherein R₁ is fluorine, chlorine orC₁-C₄-haloalkyl; R₂ is hydrogen or C₁-C₂-alkyl; R₃ is C₁-C₂-alkyl; R₄ isunsubstituted or substituted heterocyclyl, whereby the substituents areselected from the group comprising halogen, cyano and nitro, whereby ifthe number of substituents is greater than 1, the substituents may beidentical or different; Q is C₁-C₂-alkylene; X₃ and X₄ are O; and n is1;

(11) A compound of formula I, wherein R₁ is chlorine or C₁-C₂-haloalkyl;R₂ is hydrogen; R₃ is methyl; R₄ is unsubstituted or substitutedheterocyclyl, whereby the substituents are selected from the groupcomprising fluorine, chlorine or bromine, whereby if the number ofsubstituents is greater than 1, the substituents may be identical ordifferent; Q is C₁-C₂ alkylene; X₃ and X₄ are O; and n is 1;

(12) A compound of formula I, wherein R₁ is chlorine or trifluoromethyl;R₂ is hydrogen; R₃ is methyl; R₄ is unsubstituted orchlorine-substituted heterocyclyl; Q is C₁-C₂-alkylene; X₃ and X₄ are O;and n is 1;

(13) A compound of formula I, wherein R₁ is chlorine or trifluoromethyl;R₂ is hydrogen; R₃ is methyl; R₄ is pyrrolidinyl, piperidinyl, pyridyl,pyrryl, furyl, thienyl, tetrahydrofuryl, benzofuryl or benzothienyl; Qis C₁-C₂-alkylene; X₃ and X₄ are O; and n is 1.

A further object of the invention is the process for the preparation ofthe compounds of formula I and optionally the enantiomers thereof, forexample characterised in that a compound of formula

which is known or may be produced analogously to corresponding knowncompounds, and wherein R₁, R₂, X₁ and X₂ are defined as given forformula I,

a) is reacted with a compound of formula

 which is known or may be prepared analogously to corresponding knowncompounds, and wherein X₃, X₄, R₃, R₄, n and Q are defined as forformula I and Z is a leaving group, if required in the presence of abasic catalyst, or

b) is reacted with a compound of formula

 which is known or may be prepared analogously to corresponding knowncompounds, and wherein X₄, R₄, n and Q are defined as for formula I, andZ is a leaving group and X₃ is O, if required in the presence of a basiccatalyst, the nitroso group is introduced into the resulting product,optionally after isolation thereof, and the resulting oxime, optionallyafter fresh isolation, is reacted with a compound of formula

R₃X₅  V,

 which is known or may be prepared analogously to corresponding knowncompounds, and wherein X₃ is defined as for formula I and X₅ is aleaving group, if required in the presence of a basic catalyst, and theresulting product, optionally after isolation is reacted if desired witha sulphurising agent,

and if desired, a compound of formula I which is obtainable by thisprocess or in another way, or an enantiomer thereof, may be convertedinto another compound of formula I or an enantiomer thereof, a mixtureof enantiomers which is obtainable by this process is separated and thedesired enantiomer isolated.

Suitable leaving groups are halogen, C₁-C₆-alkoxy or hydroxy, preferablychlorine.

Suitable bases for facilitating the reaction are e.g. trialkylamines,basic heterocycles or phosphines. Triethylamine, diisopropylethylamine,pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine,1,5-diazabicyclo[5.4.0]undec-5-ene (DBU) and triphenylphosphine may bementioned by way of example. Diisopropylethylamine is preferred.

Suitable compositions for introducing the nitroso group are alkali metalnitrites, preferably sodium nitrite.

Suitable sulphurising compositions are sulphides of phosphoric acid,preferably P₄S₁₀.

The reaction partners can be reacted with one another as they are, i.e.without the addition of a solvent or diluent, e.g. in the melt. In mostcases, however, the addition of an inert solvent or diluent, or amixture thereof, is of advantage. Examples of such solvents or diluentsare: aromatic, aliphatic and alicyclic hydrocarbons and halogenatedhydrocarbons, such as benzene, toluene, xylene, mesitylene, tetraline,chlorobenzene, dichlorobenzene, bromobenzene, petroleum ether, hexane,cyclohexane, dichloromethane, trichloromethane, tetrachloromethane,dichloroethane, trichloroethene or tetrachloroethene; ethers, such asdiethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether,tert-butyl methyl ether, ethylene glycol monomethyl ether, ethyleneglycol monoethyl ether, ethylene glycol dimethylether,dimethoxydiethylether, tetrahydrofuran or dioxane; ketones such asacetone, methyl ethyl ketone or methyl isobutyl ketone; amides such asN,N-dimethylformamide, N,N-diethylformamide, N,N-dimethylacetamide,N-methylpyrrolidone or hexamethylphosphoric acid triamide; nitrites suchas acetonitrile or propionitrile; and sulfoxides, such as dimethylsulfoxide. If the reaction takes place in the presence of a base, thenbases used in excess, such as triethylamine, pyridine,N-methylmorpholine, or N,N-diethylaniline, can also serve as solvents ordiluents. Preferably, halogenated hydrocarbons are used, especiallydichloromethane.

The reaction which introduces the nitroso group is advantageouslycarried out in an aqueous acid. Hydrochloric and sulphuric acid are.preferred for this, especially hydrochloric acid.

The reaction is advantageously carried out in a temperature range of ca.−20° C. to ca. +150° C., preferably from ca. −10° C. to ca. +80° C.,most preferably from ca. 0° C. to ca. +40° C.

In a preferred embodiment, a compound of formula II is reacted at 0° to120°, preferably 20°, in a halogenated hydrocarbon, preferablydichloromethane, with a compound of formula III.

The compounds I may be present in the form of one of the possibleisomers or as a mixture thereof, e.g. depending on the number, absoluteand relative configurations of the asymmetric carbon atoms as pureisomers, such as antipodes and/or diastereoisomers, or as isomericmixtures, such as enantiomeric mixtures, e.g. racemates,diastereoisomeric mixtures or racemic mixtures; the invention relates toboth the pure isomers and all the possible isomeric mixtures, and is tobe understood as such hereinbefore and hereinafter, even ifstereochemical details are not specifically mentioned in each case.

Depending on the choice of starting materials and procedures,diastereoisomeric mixtures and racemic mixtures of compounds 1, whichare obtained in accordance with the invention or in another way, may beseparated in known manner into the pure diastereoisomers or racematesbased on the physical-chemical differences of the constituents, forexample by means of fractional crystallisation, distillation and/orchromatography.

Mixtures of enantiomers that are obtainable accordingly, such asracemates, may be broken down into the optical antipodes by knownmethods, for example by recrystallisation from an optically activesolvent, by chromatography on chiral adsorbents, e.g. high-pressureliquid chromatography (HPLC) on acetyl cellulose, with the assistance ofappropriate microorganisms, by cleavage with specific immobilisedenzymes, through the formation of inclusion compounds, e.g. using chiralcrown ethers, wherein only one enantiomer is complexed.

According to the invention, apart from isolation of corresponding isomermixtures, generally known methods of diastereoselective orenantioselective synthesis can also be applied to obtain purediastereoisomers or enantiomers, e.g. by carrying out the method of theinvention using educts with correspondingly suitable stereochemistry.

It is advantageous to isolate or synthesize the biologically more activeisomer in each case, e.g. enantiomer or isomer mixture, e.g. enantiomermixture, if the individual components show differences in biologicalefficacy.

In the method of the present invention, the starting materials andintermediates used are preferably those that lead to the compounds Idescribed at the beginning as being especially useful.

The invention relates especially to the method of preparation describedin the example.

Starting materials and intermediates, which are new and are usedaccording to the invention for the preparation of compounds I, as wellas their usage and process for the preparation thereof, similarly forman object of the invention.

The compounds I according to the invention are notable for their broadactivity spectrum and are valuable active ingredients for use in pestcontrol, including in particular the control of endo- and ecto-parasiteson animals, whilst being well-tolerated by warm-blooded animals, fishand plants,

In the context of the present invention, ectoparasites are understood tobe in particular insects, mites and ticks. These include insects of theorder: Lepidoptera, Coleoptera, Homoptera, Heteroptera, Diptera,Thysanoptera, Orthoptera, Anoplura, Siphonaptera, Mallophaga, Thysanura,Isoptera, Psocoptera and Hymenoptera. However, the ectoparasites whichmay be mentioned in particular are those which trouble humans or animalsand carry pathogens, for example flies such as Musca domestica, Muscavetustissima, Musca autumnalis, Fannia canicularis, Sarcophaga camaria,Lucilia cuprina, Hypoderma bovis, Hypoderma lineatum, Chrysomyiachloropyga, Dermatobia hominis, Cochliomyia hominivorax, Gasterophilusintestinalis, Oestrus ovis, Stomoxys calcitrans, Haematobia irritans andmidges (Nematocera), such as Culicidae, Simuliidae, Psychodidae, butalso blood-sucking parasites, for example fleas, such as Ctenocephalidesfelis and Ctenocephalides canis (cat and dog fleas), Xernopsyllacheopis, Pulex irritans, Dermatophilus penetrans, lice, such as Damalinaovis, Pediculus humanis, biting flies and horseflies (Tabanidae),Haematopota spp. such as Haematopota pluvialis, Tabanidea spp. such asTabanus nigrovittatus, Chrysopsinae spp. such as Chrysops caecutiens,tsetse flies, such as species of Glossinia, biting insects, particularlycockroaches, such as Blatella germanica, Blatta orientalis, Periplanetaamericana, mites, such as Dermanyssus gallinae, Sarcoptes scabiei,Psoroptes ovis and Psorergates spp. and last but not least ticks. Thelatter belong to the order Acarina. Known representatives of ticks are,for example, Boophilus, Amblyomma, Anocentor, Dermacentor,Haemaphysalis, Hyalomma, Ixodes, Rhipicentor, Margaropus, Rhipicephalus,Argas, Otobius and Omithodoros and the like, which preferably infestwarm-blooded animals including farm animals, such as cattle, pigs, sheepand goats, poultry such as chickens, turkeys and geese, fur-bearinganimals such as mink, foxes, chinchillas, rabbits and the like, as wellas domestic animals such as cats and dogs, but also humans.

Compounds I can also be used against hygiene pests, especially of theorder Diptera of the families Sarcophagidae, Anophilidae and Culicidae;the orders Orthoptera, Dictyoptera (e.g. the family Blattidae) andHymenoptera (e.g. the family Formicidae).

Compounds I also have sustainable efficacy on parasitic mites andinsects of plants. In the case of spider mites of the order Acarina,they are effective against eggs, nymphs and adults of Tetranychidae(Tetranychus spp. and Panonychus spp.).

They have high activity against sucking insects of the order Homoptera,especially against pests of the families Aphididae, Delphacidae,Cicadellidae, Psyllidae, Loccidae, Diaspididae and Eriophydidae (e.g.rust mite on citrus fruits); the orders Hemiptera, Heteroptera andThysanoptera, and on the plant-eating insects of the orders Lepidoptera,Coleoptera, Diptera and Orthoptera.

They are similarly suitable as a soil insecticide against pests in thesoil.

The compounds of formula I are therefore effective against all stages ofdevelopment of sucking insects and eating insects on crops such ascereals, cotton, rice, maize, soya, potatoes, vegetables, fruit,tobacco, hops, citrus, avocados and other crops.

The compounds of formula I are also effective against plant nematodes ofthe species Meloidogyne, Heterodera, Pratylenchus, Ditylenchus,Radopholus, Rizoglyphus etc.

In particular, the compounds are effective against helminths, in whichthe endoparasitic nematodes may be the cause of serious diseases ofmammals and poultry, e.g. sheep, pigs, goats, cattle, horses, donkeys,dogs, cats, guinea-pigs and exotic birds. Typical nematodes of thisindication are: Haemonchus, Trichostrongylus, Ostertagia, Nematodirus,Cooperia, Ascadis, Bunostonum, Oesophagostonum, Charbertia, Trichuris,Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara,Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascadis.The particular advantage of the compounds of formula I is their efficacyagainst those parasites that are resistant towards active ingredientsbased on benzimidazole.

Certain pests of the species Nematodirus, Cooperia and Oesophagostonuminfest the intestinal tract of the host animal, while others of thespecies Haemonchus and Ostertagia are parasitic in the stomach and thoseof the species Dictyocaulus are parasitic in the lung tissue. Parasitesof the families Filaridae and Setariidae may be found in the internalcell tissue and in the organs, e.g. the heart, the blood vessels, thelymph vessels and the subcutaneous tissue. A particularly notableparasite is the heartworm of the dog, Dirofilaria immitis. The compoundsof formula I are highly effective against these parasites.

Furthermore, the compounds of formula I are also especially suitable forthe control of human pathogenic parasites. Of these, typicalrepresentatives that appear in the digestive tract are those of thespecies Ancylostoma, Necator, Ascads, Strongyloides, Trichinella,Capillara, Trichuris and Enterobius. The compounds of the presentinvention are also effective against parasites of the speciesWuchereria, Brugia, Onchocerca and Loa from the family of Filariidae,which appear in the blood, in the tissue and in various organs, and alsoagainst Dracunculus and parasites of the species Strongyloides andTrichinella, which infect the gastrointestinal tract in particular.

The good pesticidal activity of the compounds of formula I correspondsto a mortality rate of at least 50-60% of the pests mentioned. Inparticular, the compounds of formula I are notable for the exceptionallylong duration of efficacy.

The activity of the compounds according to the invention and of thecompositions containing them against animal pests may be substantiallybroadened and adapted to the prevailing circumstances by adding otherinsecticides and/or acaricides. The additives in question may be forexample representatives of the following classes of active ingredient:organophosphorus compounds, nitrophenols and derivatives, formamidines,ureas, carbamates, pyrethroids, chlorinated hydrocarbons, neonicotinoidsand Bacillus thuringiensis preparations.

The compounds of formula I are preferably employed in unmodified form orpreferably together with the adjuvants conventionally used in the art offormulation and may therefore be processed in a known manner to give,for example, emulsifiable concentrates, directly sprayable or dilutablesolutions, dilute emulsions, wettable powders, soluble powders, dusts,granules or microencapsulations in polymeric substances. As with thecompositions, the methods of application, such as spraying, atomizing,dusting, scattering or pouring, are selected in accordance with theintended objectives and the prevailing circumstances.

The formulation, i.e. the agents, preparations or compositionscontaining the active ingredient of formula I, or combinations of theseactive ingredients with other agrochemical active ingredients, andoptionally a solid or liquid adjuvant, are produced in a manner knownper se, for example by intimately mixing and/or grinding the activeingredients with spreading compositions, for example with solvents,solid carriers, and optionally surface-active compounds (surfactants).

The solvents in question may be: aromatic hydrocarbons, preferablyfractions of alkylbenzenes having 8 to 12 carbon atoms, such as xylenemixtures or alkylated naphthalenes, aliphatic or cyclo-aliphatichydrocarbons, such as cyclohexane, paraffins or tetrahydronaphthalene,alcohols, such as ethanol, propanol or butanol, glycols and their ethersand esters, such as propylene glycol, dipropylene glycol ether, ethyleneglycol or ethylene glycol monomethyl or -ethyl ether, ketones, such ascyclohexanone, isophorone or diacetanol alcohol, strong polar solvents,such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide,or water, vegetable oils, such as rape, castor, coconut, or soybean oil,and also, if appropriate, silicone oils.

The solid carriers used for example for dusts and dispersible powders,are normally natural mineral fillers such as calcite, talcum, kaolin,montmorillonite or attapulgite. In order to improve the physicalproperties it is also possible to add highly dispersed silicic acid orhighly dispersed absorbent polymers. Suitable granulated adsorptivecarriers are porous types, for example pumice, broken brick, sepioliteor bentonite, and suitable non-sorbent carriers are materials such ascalcite or sand. In addition, a great number of pregranulated materialsof inorganic or organic nature can be used, e.g. especially dolomite orpulverised plant residues.

Depending on the type of active ingredient of formula I to beformulated, or the combination of these active ingredients with otherinsecticides or acaricides, suitable surface-active compounds arenon-ionic, cationic and/or anionic surfactants having good emulsifying,dispersing and wetting properties. The surfactants are also understoodto be surfactant mixtures.

Suitable anionic surfactants can be both so-called water-soluble soapsand water-soluble synthetic surfactant compounds.

Suitable soaps are the alkali metal salts, alkaline earth metal salts orunsubstituted or substituted ammonium salts of higher fatty acids(C₁₀-C₂₂), for example the sodium or potassium salts of oleic or stearicacid, or of natural fatty acid mixtures which can be obtained forexample from coconut oil or tallow oil. The fatty acid methyltaurinesalts may also be mentioned as surfactants.

More frequently, however, so-called synthetic surfactants are used,especially fatty sulphonates, fatty sulphates, sulphonated benzimidazolederivatives or alkylarylsulphonates.

The fatty sulphonates or sulphates are usually in the form of alkalimetal salts, alkaline earth metal salts or unsubstituted or substitutedammoniums salts and have an alkyl radical with 8 to 22 carbon atoms,which also includes the alkyl moiety of acyl radicals, for example, thesodium or calcium salt of ligninsulphonic acid, of dodecylsulphate or ofa mixture of fatty alcohol sulphates obtained from natural fatty acids.These compounds also comprise the salts of sulphuric acid esters andsulphonic acids of fatty alcoholethylene oxide adducts. The sulphonatedbenzimidazole derivatives preferably contain 2 sulphonic acid groups andone fatty acid radical containing 8 to 22 carbon atoms. Examples ofalkylarylsulfonates are the sodium, calcium or triethanolamine salts ofdodecylbenzenesulphonic acid, dibutyinapthalenesulphonic acid, or of anaphthalenesulphonic acid/formaldehyde condensation product. Alsosuitable are corresponding phosphates, e.g. salts of the phosphoric acidester of an adduct of p-nonylphenol with 4 to 14 moles of ethylene oxideor phospholipids.

Non-ionic surfactants are preferably polyglycol ether derivatives ofaliphatic or cycloaliphatic alcohols, or saturated or unsaturated fattyacids and alkylphenols, said derivatives containing 3 to 30 glycol ethergroups and 8 to 20 carbon atoms in the (aliphatic) hydrocarbon moietyand 6 to 18 carbon atoms in the alkyl moiety of the alkylphenols.Further suitable non-ionic surfactants are the water-soluble adducts ofpolyethylene oxide with polypropylene glycol, ethylenediaminepolypropylene glycol and alkylpolypropylene glycol containing 1 to 10carbon atoms in the alkyl chain, which adducts contain 20 to 250ethylene glycol ether groups and 10 to 100 propylene glycol ethergroups. These compounds usually contain 1 to 5 ethylene glycol units perpropylene glycol unit.

Examples of non-ionic surfactants are nonylphenolpolyethoxyethanols,castor oil polyglycol ethers, polypropylene/polyethylene oxide adducts,tributylphenoxypolyethoxyethanol, polyethylene glycol andoctylphenoxypolyethoxyethanol. Also suitable are fatty acid esters ofpolyoxyethylene sorbitan, such as polyoxyethylene sorbitan trioleate.

Cationic surfactants are preferably quaternary ammonium salts which haveas N-substituent at least one C₈-C₂₂ alkyl radical and, as furthersubstituents, lower—where appropriate—halogenated alkyl, benzyl or lowerhydroxyalkyl radicals. The salts preferably exist as halides, methylsulphates or ethyl sulphates, preferably as stearyl trimethylammoniumchloride or benzyl-di-(2-chloroethyl)-ethylammonium bromide.

The surfactants which are customary in formulation technology aredescribed for example in the following publications:

“Mc Cutcheon's Detergents and Emulsifiers Annual”, McPublishing Corp.,Glen Rock, N.J., USA, 1988”,

H. Stache, “Tensid-Taschenbuch” (Surfactants Handbook), 2^(nd) edition,C. Hanser Publishing Munich, Vienna 1981.

M. and J. Ash. “Encyclopedia of Surfactants”, Vol. I-III, ChemicalPublishing Co., New York, 1980-1981.

Preferred application forms for usage on warm-blooded animals in thecontrol of helminths include solutions, emulsions, suspensions(drenches), food additives, powders, tablets including effervescenttablets, boli, capsules, micro-capsules and pour-on formulations,whereby the physiological compatability of the formulation excipientsmust be taken into consideration.

The binders for tablets and boli may be chemically modified polymericnatural substances that are soluble in water or in alcohol, such asstarch, cellulose or protein derivatives (e.g. methyl cellulose,carboxymethyl cellulose, ethylhydroxyethyl cellulose, proteins such aszein, gelatin and the like), as well as synthetic polymers, such aspolyvinyl alcohol, polyvinyl pyrrolidone etc. The tablets also containfillers (e.g. starch, microcrystalline cellulose, sugar, lactose etc.),glidants and disintegrants.

If the anthelminthics are present in the form of feed concentrates, thenthe carriers used are e.g. performance feeds, feed grain or proteinconcentrates. Such feed concentrates or compositions may contain, apartfrom the active ingredients, also additives, vitamins, antibiotics,chemotherapeutics or other pesticides, primarily bacteriostats,fungistats, coccidiostats, or even hormone preparations, substanceshaving anabolic action or substances which promote growth, which affectthe quality of meat of animals for slaughter or which are beneficial tothe organism in another way. If the compositions or the activeingredients of formula I contained therein are added directly to feed orto the drinking troughs, then the formulated feed or drink contains theactive ingredients preferably in a concentration of ca. 0.0005 to 0.02%by weight (5-200 ppm).

Application of the compositions according to the invention to theanimals to be treated may take place topically, perorally, parenterallyor subcutaneously, the composition being present in the form ofsolutions, emulsions, suspensions, (drenches), powders, tablets, boli,capsules and pour-on formulations.

The compounds of formula I according to the invention may be used aloneor in combination with other biocides. They may be combined withpesticides having the same sphere of activity e.g. to increase activity,or with substances having another sphere of activity e.g. to broaden therange of activity. It can also be sensible to add so-called repellents.If the range of activity is to be extended to endoparasites, e.g.wormers, the compounds of formula I are suitably combined withsubstances having endoparasitic properties. Of course, they can also beused in combination with antibacterial compositions. Since the compoundsof formula I are adulticides, i.e. since they are effective inparticular against the adult stage of the target parasites, the additionof pesticides which instead attack the juvenile stages of the parasitesmay be very advantageous. In this way, the greatest part of thoseparasites that produce great economic damage will be covered. Moreover,this action will contribute substantially to avoiding the formation ofresistance. Many combinations may also lead to synergistic effects, i.e.the total amount of active ingredient can be reduced, which is desirablefrom an ecological point of view. Preferred groups of combinationpartners and especially preferred combination partners are named in thefollowing, whereby combinations may contain one or more of thesepartners in addition to a compound of formula I.

Suitable partners in the mixture may be biocides, e.g. the insecticidesand acaricides with a varying mechanism of activity, which are named inthe following and have been known to the person skilled in the art for along time, e.g. chitin synthesis inhibitors, growth regulators; activeingredients which act as juvenile hormones; active ingredients which actas adulticides; broad-band insecticides, broad-band acaricides andnematicides; and also the well known anthelminthics and insect- and/oracarid-deterring substances, said repellents or detachers.

Non-limitative examples of suitable insecticides and acaricides are:

(I) Aldicarb; (II) Azinphos- (XVI) Diflubenzuron; (XXXV) Teflubenzuron;methyl; (XVII) Endosulfan; (XXXVI) Terbufos; (III) Benfuracarb; (XVIII)Ethiofencarb; (XXXVII) Triazamate; (IV) Bifenthrin; (XIX) Fenitrothion;(XXXVIII) Abamectin; (V) Buprofezin; (XX) Fenobucarb; (XXXIX)Fenobucarb; (VI) Carbofuran; (XXI) Fenvalerate; (XL) Tebufenozide; (VII)Dibutylamino (XXII) Formothion; (XLI) Fipronil; thio; (XXIII)Methiocarb; (XLII) beta-Cyfluthrin; (VIII) Cartap; (XXIV) Heptenophos;(XLIII) Silafluofen; (IX) Chlorfluazuron; (XXV) Imidacloprid; (XLIV)Fenpyroximate; (X) Chlorpyrifos; (XXVI) Isoprocarb; (XLV) Pyridaben;(XI) Cyfluthrin; (XXVII) Methamidophos; (XLVI) Fenazaquin; (XII)Lambda-Cy- (XXVIII) Methomyl; (XLVII) Pyriproxyfen; halothrin; (XXIX)Mevinphos; (XLVIII) Pyrimidifen; (XIII) Alpha-cyper (XXX) Parathion;(XLIX) Nitenpyram; methrin; (XXXI) Parathionmethyl; (L) Ni-25, Acetami-(XIV) zeta-Cyper (XXXII) Phosalone; prid; methrin; (XXXIII) Pirimicarb;(XV) Deltamethrin; (XXXIV) Propoxur; (LII) Avermectin B₁; (LIII) aninsect-active extract from a plant; (LIV) a preparation containinginsect-active nematodes; (LV) a preparation obtained from Bacillussubtilis; (LVI) a preparation containing insect-active fungi; (LVII) apreparation containing insect-active viruses; (LIX) AC 303 630; (LXVIII)Azocyclotin; (LXXVII) Butylpyridaben; (LX) Acephat; (LXIX) Bendiocarb;(LXXVIII) Cadusafos; (LXI) Acrinathrin; (LXX) Bensultap; (LXXIX)Carbaryl; (LXII) Alanycarb; (LXXI) Betacyfluthrin; (LXXX)Carbophenthion; (LXIII) Alphamethrin; (LXXII) BPMC; (LXXXI)Chloethocarb; (LXIV) Amitraz; (LXXIII) Brofenprox; (LXXXII)Chlorethoxyfos; (LXV) Az 60541; (LXXIV) Bromophos A; (LXXXIII)Chlormephos; (LXVI) Azinphos A; (LXXV) Bufencarb; (LXXXIV)Cis-Resmethrin; (LXVII) Azinphos M; (LXXVI) Butocarboxin; (LXXXV)Clocythrin; (LXXXVI) Clofentezin; (CXVIII) Fosthiazat; (CLI) Prothoat;(LXXXVII) Cyanophos; (CXIX) Fubfenprox; (CLII) Pyrachlophos; (LXXXVIII)Cycloprothrin; (CXX) HCH; (CLIII) Pyradaphent (LXXXIX) Cyhexatin; (CXXI)Hexaflumuron; hion; (XC) Demeton M; (CXXII) Hexythiazox; (CLIV)Pyresmethrin; (XCI) Demeton S; (CXXIII) Iprobenfos; (CLV) Pyrethrum;(XCII) Demeton-S- (CXXIV) Isofenphos; (CLVI) RH 5992; methyl; (CXXV)Isoxathion; (CLVII) Salithion; (XCIII) Dichlofenthion; (CXXVI)Ivermectin; (CLVIII) Sebutos; (XCIV) Dicliphos; (CXXVII) Lambda- (CLIX)Sultotep; (XCV) Diethion; cyhalothrin; (CLX) Sulprofos; (XCVI)Dimethoat; (CXXVIII) Matathion; (CLXI) Tebufenpyrad; (XCVII)Dimethylvin- (CXXIX) Mecarbam; (CLXII) Tebupirimphos; phos; (CXXX)Mesulfenphos; (CLXIII) Tefluthrin; (XCVIII) Dioxathion; (CXXXI)Metaldehyd; (CLXIV) Temephos; (XCIX) Edifenphos; (CXXXII) Metolcarb;(CLXV) Terbam; (C) Emamectin; (CXXXIII) Milbemectin; (CLXVI) Tetrachlor-(CI) Esfenvalerat; (CXXXIV) Moxidectin; vinphos; (CII) Ethion; (CXXXV)Naled; (CLXVII) Thiafenox; (CIII) Ethofenprox; (CXXXVI) NC 184;(CLXVIII) Thiodicarb; (CIV) Ethoprophos; (CXXXVII) Omethoat; (CLXIX)Thiofanox; (CV) Etrimphos; (CXXXVIII) Oxamyl; (CLXX) Thionazin; (CVI)Fenamiphos; (CXXXIX) Oxydemethon M; (CLXXI) Thuringiensin; (CVII)Fenbutatinoxid; (CXL) Oxydeprofos; (CLXXII) Tralomethrin; (CVIII)Fenothiocarb; (CXLI) Permethrin; (CLXXIII) Triarthen; (CIX)Fenpropathrin; (CXLII) Phenthoat; (CLXXIV) Triazophos; (CX) Fenpyrad;(CXLIII) Phorat; (CLXXV) Triazuron; (CXI) Fenthion; (CXLIV) Phosmet;(CLXXVI) Trichlorfon; (CXII) Fluazinam; (CXLV) Phoxim; (CLXXVII)Triflumuron; (CXIII) Flucycloxuron; (CXLVI) Pirimiphos M; (CLXXVIII)Trimethacarb; (CXIV) Flucythrinat; (CXLVII) Pirimiphos A; (CLXXIX)Vamidothion; (CXV) Flufenoxuron; (CXLVIII) Promecarb; (CLXXX) Xylylcarb;(CXVI) Flufenprox; (CXLIX) Propaphos; (CLXXXI) YI 5301/5302; (CXVII)Fonophos; (CL) Prothiofos; (CLXXXII) Zetamethrin; (CLXXXIII) DPX-MP062;(CLXXXIV) RH-2485; (CLXXXV) D 2341; (CLXXXVI) XMC (3,5,- Xy-lyl-Methylcarbamat), (CLXXXVII) Lutenuron (CLXXXVIII) Fluazuron (CLXXXIX)Methoprene (CXC) Hydroprene (CXCI) Fenoxycarb (CXCII) Chlorfenapyr or(CXCIII) Spinosad

Non-limitative examples of suitable anthelminthics are named in thefollowing, a few representatives have insecticidal and acaricidalactivity in addition to the anthelminthic activity, and are partlyalready in the above list.

(A1)Praziquantel=2-cyclohexylcarbonyl-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-α]isoquinoline

(A2)Closantel=3,5-diiodo-N-[5-chloro-2-methyl-4-(a-cyano-4-chlorobenzyl)phenyl]salicylamide

(A3)Triclabendazole=5-chloro-6-(2,3-dichlorophenoxy)-2-methylthio-1H-benzimidazole

(A4) Levamisol=L-(−)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1b]thiazole

(A5) Mebendazole=(5-benzoyl-1H-benzimidazol-2-yl)carbaminic acidmethylester

(A6) Omphalotin=a macrocyclic fermentation product of the fungusOmphalotus olearius described in WO 97/20857

(A7) Abamectin=avermectin B1

(A8) Ivermectin=22,23-dihydroavermectin B1

(A9)Moxidectin=5-O-demethyl-28-deoxy-25-(1,3-dimethyl-1-butenyl)-6,28-epoxy-23-(methoxyimino)-milbemycinB

(A10)Doramectin=25-cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)-avermectinA1a

(A11) Milbemectin=mixture of milbemycin A3 and milbemycin A4

(A12) Milbemycinoxim=5-oxim of milbemectin

Non-limitative examples of suitable repellents and detachers are:

(R1) DEET (N,N-diethyl-m-toluamide)

(R2) KBR 3023 N-butyl-2-oxycarbonyl-(2-hydroxy)-piperidine

(R3)Cymiazole=N,-2,3-dihydro-3-methyl-1,3-thiazol-2-ylidene-2,4-xylidene

The said partners in the mixture are best known to specialists in thisfield. Most are described in various editions of the Pesticide Manual,The British Crop Protection Council, London, and others in the variouseditions of The Merck Index, Merck & Co., Inc., Rahway, N.J., USA or inpatent literature. Therefore, the following listing is restricted to afew places where they may be found by way of example.

(I) 2-Methyl-2-(methylthio)propionaldehyd-O-Methylcarbamoyloxime(Aldicarb), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 26;

(II)S(3,4-Dihydro-4-oxobenzo[d]-[1,2,3]-triazin-3-ylmethyl)O,O-dimethyl-phosphorodithioate(Azinphos-methyl), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 67;

(III)Ethyl-N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl-(methyl)aminothio]-N-isopropyl-β-alaninate(Benfuracarb), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 96;

(IV)2-Methylbiphenyl-3-ylmethyl-(Z)-(1RS)-cis-3-(2-chlor-3,3,3-trifluorprop-1-enyl)-2,2-dimethylcyclopropancarboxylate(Bifenthrin), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 118;

(V) 2-tert-Butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazian-4-one(Buprofezin), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 157;

(VI) 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl-methylcarbamate(Carbofuran), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 186;

(VII)2,3-Dihydro-2,2-dimethylbenzofuran-7-yl-(dibutylaminothio)methylcarbamate(Carbosulfan), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 188;

(VIII) S,S′-(2-Dimethylaminotrimethylene)-bis(thiocarbamate) (Cartap),from The Pesticide Manual, 11^(th)Ed. (1997), The British CropProtection Council, London, page 193;

(IX)1-[3,5-Dichloro-4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenyl]-3-(2,6-difluorobenzoyl)-urea(Chlorfluazuron), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 213;

(X) O,O-Diethyl-O-3,5,6-trichloro-2-pyridyl-phosphorothioate(Chlorpyrifos), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 235;

(XI)(RS)-α-Cyano-4-fluoro-3-phenoxybenzyl-(1RS,3RS;1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-di-methylcyclopropancarboxylate(Cyfluthrin), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 293;

(XII) Mixture of(S)-α-Cyano-3-phenoxybenzyl-(Z)-(1R,3R)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylateand(R)-α-cyano-3-phenoxybenzyl-(Z)-(1R,3R)-3-(2-chloro-3,3,3-trfluoropropenyl)-2,2-dimethylcyclopropanecarboxylate(Lambda-Cyhalothrin), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 300;

(XIII) Racemate consisting of(S)-α-cyano-3-phenoxybenzyl-(1R,3R)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylateand (R)-α-cyano-3-phenoxybenzyl-(1S,3S)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate(Alpha-cypermethrin), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 308;

(XIV) Mixture of the stereoisomers of(S)-α-cyano-3-phenoxybenzyl(1RS,3RS,1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate(zeta-Cypermethrin), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 314;

(XV)(S)-α-cyano-3-phenoxybenzyl-(1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate(Deltamethrin), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 344;

(XVI) (4-Chlorophenyl)-3-(2,6-difluorobenzoyl)urea (Diflubenzuron), fromThe Pesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 395;

(XVII)(1,4,5,6,7,7-Hexachloro-8,9,10-trinorborn-5-en-2,3-ylenbismethylene)-sulphite(Endosulfan), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 459;

(XVIII) α-Ethylthio-o-tolyl-methylcarbamate (Ethiofencarb), from ThePesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 479;

(XIX) O,O-Dimethyl-O-4-nitro-m-tolyl-phosphorothioate (Fenitrothion),from The Pesticide Manual, 11^(th)Ed. (1997), The British CropProtection Council, London, page 514;

(XX) 2-sec-Butylphenyl-methylcarbamate (Fenobucarb), from The PesticideManual, 11^(th)Ed. (1997), The British Crop Protection Council, London,page 516;

(XXI)(RS)-α-Cyano-3-phenoxybenzyl-(RS)-2-(4-chlorophenyl)-3-methylbutyrate(Fenvalerate), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 539;

(XXII) S-[Formyl(methyl)carbamoylmethyl]-O,O-dimethyl-phosphorodithioate(Formothion), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 625;

(XXIII) 4-Methylthio-3,5-xylyl-methylcarbamate (Methiocarb), from ThePesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 813;

(XXIV) 7-Chlorbicyclo[3.2.0]hepta-2,6-dien-6-yl-dimethylphosphate(Heptenophos), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 670;

(XXV) 1-(6-Chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylidenamine(Imidacloprid), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 706;

(XXVI) 2-Isopropylphenyl-methylcarbamate (Isoprocarb), from ThePesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 729;

(XXVII) O,S-Dimethyl-phosphoramidothioate (Methamidophos), from ThePesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 808;

(XXVIII) S-Methyl-N-(methylcarbarboyloxy)thioacetimidate (Methomyl),from The Pesticide Manual, 11^(th)Ed. (1997), The British CropProtection Council, London, page 815;

(XXIX) Methyl-3-(dimethoxyphosphinoyloxy)but-2-enoate (Mevinphos), fromThe Pesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 844;

(XXX) O,O-Diethyl-O-4-nitrophenyl-phosphorothioate (Parathion), from ThePesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 926;

(XXXI) O,O-Dimethyl-O-4-nitrophenyl-phosphorothioate (Parathion-methyl),from The Pesticide Manual, 11^(th)Ed. (1997), The British CropProtection Council, London, page 928;

(XXXII)S-6-Chloro-2,3-dihydro-2-oxo-1,3-benzoxazol-3-ylmethyl-O,O-diethyl-phosphordithioate(Phosalone), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 963;

(XXXIII) 2-Dimethylamino-5,6-dimethylpyrimidin-4-yl-dimethylcarbamate(Pirimicarb), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 985;

(XXXIV) 2-Isopropoxyphenyl-methylcarbamate (Propoxur), from ThePesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 1036;

(XXXV) 1-(3,5-Dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea(Teflubenzuron), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 1158;

(XXXVI) S-tert-butylthiomethyl-O,O-dimethyl-phosphorodithioate(Terbufos), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 1165;

(XXXVII)Ethyl-(3-tert.-butyl-1-dimethylcarbamoyl-1H-1,2,4-triazol-5-yl-thio)-acetate,(Triazamate), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 1224;

(XXXVIII) Abamectin, from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 3;

(XXXIX) 2-sec-butylphenyl-methylcarbamate (Fenobucarb), from ThePesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 516;

(XL) N-tert.-butyl-N-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide(Tebufenozide), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 1147;

(XLI)(±)-5-Amino-1-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)-4-trifluoromethyl-sulphinylpyrazol-3-carbonitrile(Fipronil), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 545;

(XLII)(RS)-α-cyano-4-fluoro-3-phenoxybenzyl(1RS,3RS;1RS,3RS-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate(beta-Cyfluthrin), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 295;

(XLIII)(4-Ethoxyphenyl)-[3-(4-fluoro-3-phenoxyphenyl)propyl](dimethyl)silane(Silafluofen), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 1105;

(XLIV) tert.-butyl(E)-α-(1,3-dimethyl-5-phenoxypyrazol-4-yl-methylenamino-oxy)-p-toluate(Fenpyroximate), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 530;

(XLV)2-tert.-butyl-5-(4-tert.-butylbenzylthio)-4-chloropyridazin-3(2H)-one(Pyridaben), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 1161;

(XLVI) 4-[[4-(1,1-dimethylphenyl)phenyl]ethoxy]-quinazoline(Fenazaquin), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 507;

(XLVII) 4-Phenoxyphenyl-(RS)-2-(pyridyloxy)propyl-ether (Pyriproxyfen),from The Pesticide Manual, 11^(th)Ed. (1997), The British CropProtection Council, London, page 1073;

(XLVIII)5-Chloro-N{2-[4-(2-ethoxyethyl)-2,3-dimethylphenoxy]ethyl}-6-ethylpyrimidin-4-amine(Pyrimidifen), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 1070;

(XLIX)(E)-N-(6-chloro-3-pyrdylmethyl)-N-ethyl-N′-methyl-2-nitrovinylidenediamine(Nitenpyram), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 880;

(L) (E)-N¹-[(6-chloro-3-pyridyl)methyl]-N²-cyano-N¹-methylacetamidine(NI-25, Acetamiprid), from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 9;

(LI) Avermectin B₁, from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 3;

(LII) an insect-active extract from a plant, especially(2R,6aS,12aS)-1,2,6,6a,12,12a-hexhydro-2-isopropenyl-8,9-dimethoxy-chromeno[3,4-b]furo[2,3-h]chromen-6-one(Rotenone), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 1097; and an extract fromAzadirachta indica, especially azadirachtin, from The Pesticide Manual,11^(th)Ed. (1997), The British Crop Protection Council, London, page 59;and

(LIII) a preparation which contains insect-active nematodes, preferablyHeterorhabditis bacteriophora and Heterorhabditis megidis, from ThePesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 671; Steinernema feltiae, from The PesticideManual, 11^(th)Ed. (1997), The British Crop Protection Council, London,page 1115 and Steinernema scapterisci, from The Pesticide Manual,11^(th)Ed. (1997), The British Crop Protection Council, London, page1116;

(LIV) a preparation obtainable from Bacillus subtilis, from ThePesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 72; or from a strain of Bacillus thuringiensiswith the exception of compounds isolated from GC91 or from NCTC11821;The Pesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 73;

(LV) a preparation which contains insect-active fungi, preferablyVerticillium lecanii, from The Pesticide Manual, 11^(th)Ed. (1997), TheBritish Crop Protection Council, London, page 1266; Beauveriabrogniartii, from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 85 and Beauveria bassiana, fromThe Pesticide Manual, 11^(th)Ed. (1997), The British Crop ProtectionCouncil, London, page 83;

(LVI) a preparation which contains insect-active viruses, preferablyNeodipridon Sertifer NPV, from The Pesticide Manual, 11^(th)Ed. (1997),The British Crop Protection Council, London, page 1342; Mamestrabrassicae NPV, from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 759 and Cydia pomonella granulosisvirus, from The Pesticide Manual, 11^(th)Ed. (1997), The British CropProtection Council, London, page 291;

(CLXXXI)7-Chloro-2,3,4a,5-tetrahydro-2-[methoxycarbonyl(4-trifluoromethoxyphenyl)carbamoyl]indole[1,2e]oxazolin-4a-carboxylate(DPX-MP062,Indoxycarb), from The Pesticide Manual, 11^(th)Ed. (1997), The BritishCrop Protection Council, London, page 453;

(CLXXXII)N′-tert.-butyl-N′-(3,5-dimethylbenzoyl)-3-methoxy-2-methylbenzohydrazide(RH-2485, Methoxyfenozide), from The Pesticide Manual, 11^(th)Ed.(1997), The British Crop Protection Council, London, page 1094; and

(CLXXXIII) (N′-[4-methoxy-biphenyl-3-yl]-hydrazinecarboxylic acidisopropyl ester (D 2341), from Brighton Crop Protection Conference,1996, 487-493;

(R2) Book of Abstracts, 212th ACS National Meeting Orlando, Fla., Aug.25-29 (1996), AGRO-020. Publisher American Chemical Society, Washington,D.C. CONEN: 63BFAF.

As a consequence of the above details, a further essential aspect of thepresent invention relates to combination preparations for the control ofparasites on warm-blooded animals, characterised in that they contain,in addition to a compound of formula I, at least one further activeingredient having the same or different sphere of activity and at leastone physiologically acceptable carrier. The present invention is notrestricted to two-fold combinations.

As a rule, the anthelminthic compositions according to the inventioncontain 0.1 to 99% by weight, especially 0.1 to 95% by weight of activeingredient of formula I, Ia or mixtures thereof, 99.9 to 1% by weight,especially 99.8 to 5% by weight of a solid or liquid admixture,including 0 to 25% by weight, especially 0.1 to 25% by weight of asurfactant.

The pour-on or spot-on method consists in applying the compound offormula I to a specific location of the skin or coat, advantageously tothe neck or backbone of the animal. This takes place e.g. by applying aswab or spray of the pour-on or spot-on formulation to a relativelysmall area of the coat, from where the active substance is dispersedalmost automatically over wide areas of the fur owing to the spreadingnature of the components in the formulaton and assisted by the animal'smovements.

Pour-on or spot-on formulations suitably contain carriers, which promoterapid dispersement over the skin surface or in the coat of the hostanimal, and are generally regarded as spreading oils. Suitable carriersare e.g. oily solutions; alcoholic and isopropanolic solutions such assolutions of 2-octyidodecanol or oleyl alcohol; solutions in esters ofmonocarboxylic acids, such as isopropyl myristate, isopropyl palmitate,lauric acid oxalate, oleic acid oleyl ester, oleic acid decyl ester,hexyl laurate, oleyl oleate, decyl oleate, capric acid esters ofsaturated fat alcohols of chain length C₁₂-C₁₈; solutions of esters ofdicarboxylic acids, such as dibutyl phthalate, diisopropyl isophthalate,adipic acid diisopropyl ester, di-n-butyl adipate or also solutions ofesters of aliphatic acids, e.g. glycols. It may be advantageous for adispersing agent to be additionally present, such as one known from thepharmaceutical or cosmetic industry. Examples are 2-pyrrolidone,2-(N-alkyl)pyrrolidone, acetone, polyethylene glycol and the ethers andesters thereof, propylene glycol or synthetic triglycerides.

The oily solutions include e.g. vegetable oils such as olive oil,groundnut oil, sesame oil, pine oil, linseed oil or castor oil. Thevegetable oils may also be present in epoxidised form. Paraffins andsilicone oils may also be used.

A pour-on or spot-on formulation generally contains 1 to 20% by weightof a compound of formula I, 0.1 to 50% by weight of dispersing agent and45 to 98.9% by weight of solvent.

The pour-on or spot-on method is especially advantageous for use on herdanimals such as cattle, horses, sheep or pigs, in which it is difficultor time-consuming to treat all the animals orally or by injection.Because of its simplicity, this method can of course also be used forall other animals, including individual domestic animals or pets, and isgreatly favoured by the keepers of the animals, as it can often becarried out without the specialist presence of the veterinarian.

Whereas it is preferred to formulate commercial products asconcentrates, the end user will normally use dilute formulations.

Such compositions may also contain further additives, such asstabilisers, anti-foaming agents, viscosity regulators, binding agentsor tackifiers, as well as other active ingredients, in order to achievespecial effects.

Anthelminthic compositions of this type, which are used by the end user,similarly form a constituent of the present invention.

In each of the processes according to the invention for pest control orin each of the pest control compositions according to the invention, theactive ingredients of formula I can be used in all of their stericconfigurations or in mixtures thereof.

The invention also includes a method of prophylactically protectingwarm-blooded animals, especially productive livestock, domestic animalsand pets, against parasitic helminths, which is characterised in thatthe active ingredients of formula I or the active ingredientformulations prepared therefrom are administered to the animals as anadditive to the feed, or to the drinks or also in solid or liquid form,orally or by injection or parenterally. The invention also includes thecompounds of formula I according to the invention for usage in one ofthe said processes.

The following examples serve merely to illustrate the invention withoutrestricting it, the term active ingredient representing a substancelisted in table 1.

In particular, preferred formulations are made up as follows:

(%=percent by weight)

FORMULATION EXAMPLES

1. Emulsion concentrates a) b) c) active ingredient 25% 40% 50% Cadodecylbenzene sulphonate  5%  8%  6% castor oil polyethylene glycolether  5% — — (36 mols ethylene oxide) tributylphenolpolyethylene glycolether — 12%  4% (30 mols ethylene oxide) cyclohexanone — 15% 20% xylenemixture 65% 25% 20%

From these concentrates, emulsions of any desired concentration may beprepared by diluting with water.

2. Emulsion concentrates a) b) c) active ingredient 10% 8% 60%octylphenol polyethylene glycol ether  3% 3%  2% (4-5 mols ethyleneoxide) Ca dodecylbenzene sulphonate  3% 4%  4% castor oil polyethyleneglycol ether  4% 5%  4% (35 mols ethylene oxide) cyclohexanone 30% 40% 15% xylene mixture 50% 40%  15%

From these concentrates, emulsions of any desired concentration may beprepared by diluting with water.

3. Suspension concentrate active ingredient 40% ethylene glycol 10%nonylphenol polyethylene glycol ether (15 mols ethylene oxide)  6% Naligninsulphonate 10% carboxymethylcellulose 1% 37% aqueous formaldehydesolution 0.2%  silicone oil in the form of a 75% aqueous emulsion 0.8% water 32%

The finely ground active ingredient is intimately mixed with theadmixtures. In this way, a suspension concentrate is obtained, fromwhich suspensions of any desired concentration can be prepared bydiluting with water.

4. Powder mixtures that are dispersible in water a) b) c) activeingredient 25% 50% 75% Na ligninsulphonate  5%  5% — oleic acid  3% — 5% Na diisobutylnaphthalene sulphonate —  6% 10% octylphenolpolyethylene glycol ether (7-8 mols ethylene oxide) —  2% — highlydispersed silicic acid  5% 10% 10% kaolin 62% 27% —

The active ingredient is mixed thoroughly with the admixtures and groundwell in an appropriate mill. Wettable powders are obtained, which may bediluted with water to form suspensions of any desired concentration.

5. Dusts a) b) active ingredient  2% 5% highly dispersed silicic acid 1% 5% talc 97% — kaolin — 90% 

By intimately mixing the carriers with the active ingredient andgrinding the mixture, ready-to-use dusts are obtained.

6. Granulate a) b) active ingredient  5% 10% kaolin 94% — highlydispersed silicic acid  1% — attapulgite — 90%

The active ingredient is dissolved in methylene chloride, sprayed ontothe carrier and the solvent subsequently concentrated by evaporationunder vacuum. Granulates of this kind can be mixed with the fodder.

7. Granulate active ingredient 10% Na ligninsulphonate  2%carboxymethylcellulose  1% kaolin 87%

The active ingredient is mixed with the admixtures, ground and moistenedwith water. This mixture is extruded and then dried in a stream of air.

8. Granulate active ingredient 3% polyethylene glycol (mw 200) 3% kaolin94%  (mw = molecular weight)

The finely ground active ingredient is evenly applied in a mixer to thekaolin which has been moistened with polyethylene glycol. In this way,dust-free coated granules are obtained.

9. Tablets or boli I active ingredient 33.00% methylcellulose 0.80%silicic acid, highly dispersed 0.80% corn starch 8.40% II lactose,cryst. 22.50% corn starch 17.00% microcryst. cellulose 16.50% magnesiumstearate 1.00%

I Methyl cellulose is stirred into water. After the material hasswollen, silicic acid is stirred in and the mixture homogeneouslysuspended. The active ingredient and the corn starch are mixed. Theaqueous suspension is worked into this mixture and kneaded to a dough.The resulting mass is granulated through a 12 M sieve and dried.

II All 4 excipients are mixed thoroughly.

III The preliminary mixes obtained according to I and II are mixed andpressed into tablets or boli.

10. Injectables A. Oily vehicle (slow release) 1. active ingredient0.1-1.0 g groundnut oil ad 100 ml 2. active ingredient 0.1-1.0 g sesameoil ad 100 ml

Preparation: The active ingredient is dissolved in part of the oilwhilst stirring and, if required, with gentle heating, then aftercooling made up to the desired volume and sterile-filtered through asuitable membrane filter with a pore size of 0.22 mm.

B Water-miscible solvent (average rate of release) active ingredient0.1-1.0 g 4-hydroxymethyl-1,3-dioxolane (glycerol formal) 40 g1,2-propanediol ad 100 ml an active ingredient 0.1-1.0 g glyceroldimethyl ketal 40 g 1,2-propanediol ad 100 ml

Preparation: The active ingredient is dissolved in part of the solventwhilst stirring, made up to the desired volume and sterile-filteredthrough a suitable membrane filter with a pore size of 0.22 mm.

C. Aqueous solubilisate (rapid release) 1. active ingredient 0.1-1.0 gpolyethoxylated castor oil (40 ethylene oxide units) 10 g1,2-propanediol 20 g benzyl alcohol  1 g Aqua ad inject. ad 100 ml 2.active ingredient 0.1-1.0 g polyethoxylated sorbitan monooleate (20ethylene  8 g oxide units) 4-hydroxymethyl-1,3-dioxolane (glycerolformal) 20 g benzyl alcohol  1 g Aqua ad inject. ad 100 ml

Preparation: The active ingredient is dissolved in the solvents and thesurfactant, and made up with water to the desired volume. Sterilefiltration through an appropriate membrane filter of 0.22 mm pore size.

11. Pour on A. active ingredient 5 g isopropyl myristate 10 g isopropanol ad 100 ml B active ingredient 2 g hexyl laurate 5 gmedium-chained triglycerides 15 g  ethanol ad 100 ml C. activeingredient 2 g oleyl oleate 5 g N-methyl-pyrrolidone 40 g  isopropanolad 100 ml

The aqueous systems may also preferably be used for oral and/orintraruminal application.

The compositions may also contain further additives, such asstabilisers, e.g. where appropriate epoxidised vegetable oils(epoxidised coconut oil, rapeseed oil, or soybean oil); antifoams,typically silicone oil, preservatives, viscosity regulators, binders,tackifiers, as well as fertilisers or other chemical agents to achievespecial effects.

Further biologically active substances or additives, which are neutraltowards the compounds of formula I and do not have a harmful effect onthe host animal to be treated, as well as mineral salts or vitamins, mayalso be added to the described compositions.

The following examples serve to illustrate the invention. They do notlimit the invention. The letter ‘h’ stands for hour.

PREPARATION EXAMPLEN-(5-Cyano-4-trifluoromethylthiazol-2-yl)-2-(2,4-dichlorophenoxy)-1-methoximinobutyricAcid Amide

1 drop of dimethylformamide and 283 mg of oxalyl chloride are added to asolution of 500 mg of 2-(2,4-dichlorophenoxy)-1-methoximinobutyric acidin 10 ml of dichloromethane, and stirred first of all for 10 minutes atroom temperature, and then for a further 10 minutes under reflux. Thereaction mixture is subsequently concentrated under vacuum, diluted with4 ml of dichloromethane, and added dropwise to a solution of 223 mg oftriethylamine and 330 mg of 2-amino-5-cyano-4-trifluoromethylthiazole in20 ml of tetrahydrofuran. After stirring for 12 hours at roomtemperature, the mixture is concentrated by evaporation under vacuum,and the residue chromatographed on a column of silica gel withhexane/ethyl acetate (5:1), whereby the product is obtained as a waxycompound.

The substances named in the following table may also be preparedanalogously to the above-described method. The values of the meltingpoints are given in ° C.

TABLE 1

No. X₁ X₂ R₁ R₂ R₅ (R₉)m phys. data 1.1 N N Cl H H H 1.2 N N Cl H H 2-F1.3 N N Cl H H 4-F 1.4 N N Cl H H 2,4-F₂ 1.5 N N Cl H H 2-Cl 1.6 N N ClH H 4-Cl 1.7 N N Cl H H 2,4-Cl₂ 1.8 N N Cl H H 4-CF₃ 1.9 N N Cl H H 4-CN1.10 N N Cl H H 4-phenoxy 1.11 N N Cl H CH₃ H 1.12 N N Cl H CH₃ 2-F 1.13N N Cl H CH₃ 4-F 1.14 N N Cl H CH₃ 2,4-F₂ 1.15 N N Cl H CH₃ 2-Cl 1.16 NN Cl H CH₃ 4-Cl 1.17 N N Cl H CH₃ 2,4-Cl₂ 1.18 N N Cl H CH₃ 4-CF₃ 1.19 NN Cl H CH₃ 4-CN 1.20 N N Cl H CH₃ 4-phenoxy 1.21 N N Cl CH₃ H H 1.22 N NCl CH₃ H 2-F 1.23 N N Cl CH₃ H 4-F 1.24 N N Cl CH₃ H 2,4-F₂ 1.25 N N ClCH₃ H 2-Cl 1.26 N N Cl CH₃ H 4-Cl 1.27 N N Cl CH₃ H 2,4-Cl₂ 1.28 N N ClCH₃ H 4-CF₃ 1.29 N N Cl CH₃ H 4-CN 1.30 N N Cl CH₃ H 4-phenoxy 1.31 N NCl CH₃ CH₃ H 1.32 N N Cl CH₃ CH₃ 2-F 1.33 N N Cl CH₃ CH₃ 4-F 1.34 N N ClCH₃ CH₃ 2,4-F₂ 1.35 N N Cl CH₃ CH₃ 2-Cl 1.36 N N Cl CH₃ CH₃ 4-Cl 1.37 NN Cl CH₃ CH₃ 2,4-Cl₂ 1.38 N N Cl CH₃ CH₃ 4-CF₃ 1.39 N N Cl CH₃ CH₃ 4-CN1.40 N N Cl CH₃ CH₃ 4-phenoxy 1.41 N N CF₃ H H H 1.42 N N CF₃ H H 2-F1.43 N N CF₃ H H 4-F 1.44 N N CF₃ H H 2,4-F₂ 1.45 N N CF₃ H H 2-Cl 1.46N N CF₃ H H 4-Cl 1.47 N N CF₃ H H 2,4-Cl₂ 1.48 N N CF₃ H H 4-CF₃ 1.49 NN CF₃ H H 4-CN 1.50 N N CF₃ H H 4-phenoxy 1.51 N N CF₃ H CH₃ H 1.52 N NCF₃ H CH₃ 2-F 1.53 N N CF₃ H CH₃ 4-F 1.54 N N CF₃ H CH₃ 2,4-F₂ 1.55 N NCF₃ H CH₃ 2-Cl 1.56 N N CF₃ H CH₃ 4-Cl 1.57 N N CF₃ H CH₃ 2,4-Cl₂ 1.58 NN CF₃ H CH₃ 4-CF₃ 1.59 N N CF₃ H CH₃ 4-CN 1.60 N N CF₃ H CH₃ 4-phenoxy1.61 N N CF₃ CH₃ H H 1.62 N N CF₃ CH₃ H 2-F 1.63 N N CF₃ CH₃ H 4-F 1.64N N CF₃ CH₃ H 2,4-F₂ 1.65 N N CF₃ CH₃ H 2-Cl 1.66 N N CF₃ CH₃ H 4-Cl1.67 N N CF₃ CH₃ H 2,4-Cl₂ 1.68 N N CF₃ CH₃ H 4-CF₃ 1.69 N N CF₃ CH₃ H4-CN 1.70 N N CF₃ CH₃ H 4-phenoxy 1.71 N N CF₃ CH₃ CH₃ H 1.72 N N CF₃CH₃ CH₃ 2-F 1.73 N N CF₃ CH₃ CH₃ 4-F 1.74 N N CF₃ CH₃ CH₃ 2,4-F₂ 1.75 NN CF₃ CH₃ CH₃ 2-Cl 1.76 N N CF₃ CH₃ CH₃ 4-Cl 1.77 N N CF₃ CH₃ CH₃2,4-Cl₂ 1.78 N N CF₃ CH₃ CH₃ 4-CF₃ 1.79 N N CF₃ CH₃ CH₃ 4-CN 1.80 N NCF₃ CH₃ CH₃ 4-phenoxy 1.81 N C(CN) Cl H H H 1.82 N C(CN) Cl H H 2-F 1.83N C(CN) Cl H H 4-F 1.84 N C(CN) Cl H H 2,4-F₂ 1.85 N C(CN) Cl H H 2-Cl1.86 N C(CN) Cl H H 4-Cl 1.87 N C(CN) Cl H H 2,4-Cl₂ 1.88 N C(CN) Cl H H4-CF₃ 1.89 N C(CN) Cl H H 4-CN 1.90 N C(CN) Cl H H 4-phenoxy 1.91 NC(CN) Cl H CH₃ H 1.92 N C(CN) Cl H CH₃ 2-F 1.93 N C(CN) Cl H CH₃ 4-F1.94 N C(CN) Cl H CH₃ 2,4-F₂ 1.95 N C(CN) Cl H CH₃ 2-Cl 1.96 N C(CN) ClH CH₃ 4-Cl 1.97 N C(CN) Cl H CH₃ 2,4-Cl₂ 1.98 N C(CN) Cl H CH₃ 4-CF₃1.99 N C(CN) Cl H CH₃ 4-CN 1.100 N C(CN) Cl H CH₃ 4-phenoxy 1.101 NC(CN) Cl CH₃ H H 1.102 N C(CN) Cl CH₃ H 2-F 1.103 N C(CN) Cl CH₃ H 4-F1.104 N C(CN) Cl CH₃ H 2,4-F₂ 1.105 N C(CN) Cl CH₃ H 2-Cl 1.106 N C(CN)Cl CH₃ H 4-Cl 1.107 N C(CN) Cl CH₃ H 2,4-Cl₂ 1.108 N C(CN) Cl CH₃ H4-CF₃ 1.109 N C(CN) Cl CH₃ H 4-CN 1.110 N C(CN) Cl CH₃ H 4-phenoxy 1.111N C(CN) Cl CH₃ CH₃ H 1.112 N C(CN) Cl CH₃ CH₃ 2-F 1.113 N C(CN) Cl CH₃CH₃ 4-F 1.114 N C(CN) Cl CH₃ CH₃ 2,4-F₂ 1.115 N C(CN) Cl CH₃ CH₃ 2-Cl1.116 N C(CN) Cl CH₃ CH₃ 4-Cl 1.117 N C(CN) Cl CH₃ CH₃ 2,4-Cl₂ 1.118 NC(CN) Cl CH₃ CH₃ 4-CF₃ 1.119 N C(CN) Cl CH₃ CH₃ 4-CN 1.120 N C(CN) ClCH₃ CH₃ 4-phenoxy 1.121 N C(CN) CF₃ H H H 1.122 N C(CN) CF₃ H H 2-F1.123 N C(CN) CF₃ H H 4-F 1.124 N C(CN) CF₃ H H 2,4-F₂ 1.125 N C(CN) CF₃H H 2-Cl 1.126 N C(CN) CF₃ H H 4-Cl 1.127 N C(CN) CF₃ H H 2,4-Cl₂ 1.128N C(CN) CF₃ H H 4-CF₃ 1.129 N C(CN) CF₃ H H 4-CN 1.130 N C(CN) CF₃ H H4-phenoxy 1.131 N C(CN) CF₃ H CH₃ H 1.132 N C(CN) CF₃ H CH₃ 2-F 1.133 NC(CN) CF₃ H CH₃ 4-F 1.134 N C(CN) CF₃ H CH₃ 2,4-F₂ 1.135 N C(CN) CF₃ HCH₃ 2-Cl 1.136 N C(CN) CF₃ H CH₃ 4-Cl 1.137 N C(CN) CF₃ H CH₃ 2,4-Cl₂waxy 1.138 N C(CN) CF₃ H CH₃ 4-CF₃ 1.139 N C(CN) CF₃ H CH₃ 4-CN 1.140 NC(CN) CF₃ H CH₃ 4-phenoxy 1.141 N C(CN) CF₃ CH₃ H H 1.142 N C(CN) CF₃CH₃ H 2-F 1.143 N C(CN) CF₃ CH₃ H 4-F 1.144 N C(CN) CF₃ CH₃ H 2,4-F₂1.145 N C(CN) CF₃ CH₃ H 2-Cl 1.146 N C(CN) CF₃ CH₃ H 4-Cl 1.147 N C(CN)CF₃ CH₃ H 2,4-Cl₂ 1.148 N C(CN) CF₃ CH₃ H 4-CF₃ 1.149 N C(CN) CF₃ CH₃ H4-CN 1.150 N C(CN) CF₃ CH₃ H 4-phenoxy 1.151 N C(CN) CF₃ CH₃ CH₃ H 1.152N C(CN) CF₃ CH₃ CH₃ 2-F 1.153 N C(CN) CF₃ CH₃ CH₃ 4-F 1.154 N C(CN) CF₃CH₃ CH₃ 2,4-F₂ 1.155 N C(CN) CF₃ CH₃ CH₃ 2-Cl 1.156 N C(CN) CF₃ CH₃ CH₃4-Cl 1.157 N C(CN) CF₃ CH₃ CH₃ 2,4-Cl₂ 1.158 N C(CN) CF₃ CH₃ CH₃ 4-CF₃1.159 N C(CN) CF₃ CH₃ CH₃ 4-CN 1.160 N C(CN) CF₃ CH₃ CH₃ 4-phenoxy 1.161C(CN) N Cl H H H 1.162 C(CN) N Cl H H 2-F 1.163 C(CN) N Cl H H 4-F 1.164C(CN) N Cl H H 2,4-F₂ 1.165 C(CN) N Cl H H 2-Cl 1.166 C(CN) N Cl H H4-Cl 1.167 C(CN) N Cl H H 2,4-Cl₂ 1.168 C(CN) N Cl H H 4-CF₃ 1.169 C(CN)N Cl H H 4-CN 1.170 C(CN) N Cl H H 4-phenoxy 1.171 C(CN) N Cl H CH₃ H1.172 C(CN) N Cl H CH₃ 2-F 1.173 C(CN) N Cl H CH₃ 4-F 1.174 C(CN) N Cl HCH₃ 2,4-F₂ 1.175 C(CN) N Cl H CH₃ 2-Cl 1.176 C(CN) N Cl H CH₃ 4-Cl 1.177C(CN) N Cl H CH₃ 2,4-Cl₂ 140-141° C. 1.178 C(CN) N Cl H CH₃ 4-CF₃ 1.179C(CN) N Cl H CH₃ 4-CN 1.180 C(CN) N Cl H CH₃ 4-phenoxy 1.181 C(CN) N ClCH₃ H H 1.182 C(CN) N Cl CH₃ H 2-F 1.183 C(CN) N Cl CH₃ H 4-F 1.184C(CN) N Cl CH₃ H 2,4-F₂ 1.185 C(CN) N Cl CH₃ H 2-Cl 1.186 C(CN) N Cl CH₃H 4-Cl 1.187 C(CN) N Cl CH₃ H 2,4-Cl₂ 1.188 C(CN) N Cl CH₃ H 4-CF₃ 1.189C(CN) N Cl CH₃ H 4-CN 1.190 C(CN) N Cl CH₃ H 4-phenoxy 1.191 C(CN) N ClCH₃ CH₃ H 1.192 C(CN) N Cl CH₃ CH₃ 2-F 1.193 C(CN) N Cl CH₃ CH₃ 4-F1.194 C(CN) N Cl CH₃ CH₃ 2,4-F₂ 1.195 C(CN) N Cl CH₃ CH₃ 2-Cl 1.196C(CN) N Cl CH₃ CH₃ 4-Cl 1.197 C(CN) N Cl CH₃ CH₃ 2,4-Cl₂ 1.198 C(CN) NCl CH₃ CH₃ 4-CF₃ 1.199 C(CN) N Cl CH₃ CH₃ 4-CN 1.200 C(CN) N Cl CH₃ CH₃4-phenoxy 1.201 C(CN) N CF₃ H H H 1.202 C(CN) N CF₃ H H 2-F 1.203 C(CN)N CF₃ H H 4-F 1.204 C(CN) N CF₃ H H 2,4-F₂ 1.205 C(CN) N CF₃ H H 2-Cl1.206 C(CN) N CF₃ H H 4-Cl 1.207 C(CN) N CF₃ H H 2,4-Cl₂ 1.208 C(CN) NCF₃ H H 4-CF₃ 1.209 C(CN) N CF₃ H H 4-CN 1.210 C(CN) N CF₃ H H 4-phenoxy1.211 C(CN) N CF₃ H CH₃ H 1.212 C(CN) N CF₃ H CH₃ 2-F 1.213 C(CN) N CF₃H CH₃ 4-F 1.214 C(CN) N CF₃ H CH₃ 2,4-F₂ 1.215 C(CN) N CF₃ H CH₃ 2-Cl1.216 C(CN) N CF₃ H CH₃ 4-Cl 1.217 C(CN) N CF₃ H CH₃ 2,4-Cl₂ 1.218 C(CN)N CF₃ H CH₃ 4-CF₃ 1.219 C(CN) N CF₃ H CH₃ 4-CN 1.220 C(CN) N CF₃ H CH₃4-phenoxy 1.221 C(CN) N CF₃ CH₃ H H 1.222 C(CN) N CF₃ CH₃ H 2-F 1.223C(CN) N CF₃ CH₃ H 4-F 1.224 C(CN) N CF₃ CH₃ H 2,4-F₂ 1.225 C(CN) N CF₃CH₃ H 2-Cl 1.226 C(CN) N CF₃ CH₃ H 4-Cl 1.227 C(CN) N CF₃ CH₃ H 2,4-Cl₂1.228 C(CN) N CF₃ CH₃ H 4-CF₃ 1.229 C(CN) N CF₃ CH₃ H 4-CN 1.230 C(CN) NCF₃ CH₃ H 4-phenoxy 1.231 C(CN) N CF₃ CH₃ CH₃ H 1.232 C(CN) N CF₃ CH₃CH₃ 2-F 1.233 C(CN) N CF₃ CH₃ CH₃ 4-F 1.234 C(CN) N CF₃ CH₃ CH₃ 2,4-F₂1.235 C(CN) N CF₃ CH₃ CH₃ 2-Cl 1.236 C(CN) N CF₃ CH₃ CH₃ 4-Cl 1.237C(CN) N CF₃ CH₃ CH₃ 2,4-Cl₂ 1.238 C(CN) N CF₃ CH₃ CH₃ 4-CF₃ 1.239 C(CN)N CF₃ CH₃ CH₃ 4-CN 1.240 C(CN) N CF₃ CH₃ CH₃ 4-phenoxy 1.241 C(CN) C(CN)Cl H H H 1.242 C(CN) C(CN) Cl H H 2-F 1.243 C(CN) C(CN) Cl H H 4-F 1.244C(CN) C(CN) Cl H H 2,4-F₂ 1.245 C(CN) C(CN) Cl H H 2-Cl 1.246 C(CN)C(CN) Cl H H 4-Cl 1.247 C(CN) C(CN) Cl H H 2,4-Cl₂ 1.248 C(CN) C(CN) ClH H 4-CF₃ 1.249 C(CN) C(CN) Cl H H 4-CN 1.250 C(CN) C(CN) Cl H H4-phenoxy 1.251 C(CN) C(CN) Cl H CH₃ H 1.252 C(CN) C(CN) Cl H CH₃ 2-F1.253 C(CN) C(CN) Cl H CH₃ 4-F 1.254 C(CN) C(CN) Cl H CH₃ 2,4-F₂ 1.255C(CN) C(CN) Cl H CH₃ 2-Cl 1.256 C(CN) C(CN) Cl H CH₃ 4-Cl 1.257 C(CN)C(CN) Cl H CH₃ 2,4-Cl₂ 1.258 C(CN) C(CN) Cl H CH₃ 4-CF₃ 1.259 C(CN)C(CN) Cl H CH₃ 4-CN 1.260 C(CN) C(CN) Cl H CH₃ 4-phenoxy 1.261 C(CN)C(CN) Cl CH₃ H H 1.262 C(CN) C(CN) Cl CH₃ H 2-F 1.263 C(CN) C(CN) Cl CH₃H 4-F 1.264 C(CN) C(CN) Cl CH₃ H 2,4-F₂ 1.265 C(CN) C(CN) Cl CH₃ H 2-Cl1.266 C(CN) C(CN) Cl CH₃ H 4-Cl 1.267 C(CN) C(CN) Cl CH₃ H 2,4-Cl₂ 1.268C(CN) C(CN) Cl CH₃ H 4-CF₃ 1.269 C(CN) C(CN) Cl CH₃ H 4-CN 1.270 C(CN)C(CN) Cl CH₃ H 4-phenoxy 1.271 C(CN) C(CN) Cl CH₃ CH₃ H 1.272 C(CN)C(CN) Cl CH₃ CH₃ 2-F 1.273 C(CN) C(CN) Cl CH₃ CH₃ 4-F 1.274 C(CN) C(CN)Cl CH₃ CH₃ 2,4-F₂ 1.275 C(CN) C(CN) Cl CH₃ CH₃ 2-Cl 1.276 C(CN) C(CN) ClCH₃ CH₃ 4-Cl 1.277 C(CN) C(CN) Cl CH₃ CH₃ 2,4-Cl₂ 1.278 C(CN) C(CN) ClCH₃ CH₃ 4-CF₃ 1.279 C(CN) C(CN) Cl CH₃ CH₃ 4-CN 1.280 C(CN) C(CN) Cl CH₃CH₃ 4-phenoxy 1.281 C(CN) C(CN) CF₃ H H H 1.282 C(CN) C(CN) CF₃ H H 2-F1.283 C(CN) C(CN) CF₃ H H 4-F 1.284 C(CN) C(CN) CF₃ H H 2,4-F₂ 1.285C(CN) C(CN) CF₃ H H 2-Cl 1.286 C(CN) C(CN) CF₃ H H 4-Cl 1.287 C(CN)C(CN) CF₃ H H 2,4-Cl₂ 1.288 C(CN) C(CN) CF₃ H H 4-CF₃ 1.289 C(CN) C(CN)CF₃ H H 4-CN 1.290 C(CN) C(CN) CF₃ H H 4-phenoxy 1.291 C(CN) C(CN) CF₃ HCH₃ H 1.292 C(CN) C(CN) CF₃ H CH₃ 2-F 1.293 C(CN) C(CN) CF₃ H CH₃ 4-F1.294 C(CN) C(CN) CF₃ H CH₃ 2,4-F₂ 1.295 C(CN) C(CN) CF₃ H CH₃ 2-Cl1.296 C(CN) C(CN) CF₃ H CH₃ 4-Cl 1.297 C(CN) C(CN) CF₃ H CH₃ 2,4-Cl₂1.298 C(CN) C(CN) CF₃ H CH₃ 4-CF₃ 1.299 C(CN) C(CN) CF₃ H CH₃ 4-CN 1.300C(CN) C(CN) CF₃ H CH₃ 4-phenoxy 1.301 C(CN) C(CN) CF₃ CH₃ H H 1.302C(CN) C(CN) CF₃ CH₃ H 2-F 1.303 C(CN) C(CN) CF₃ CH₃ H 4-F 1.304 C(CN)C(CN) CF₃ CH₃ H 2,4-F₂ 1.305 C(CN) C(CN) CF₃ CH₃ H 2-Cl 1.306 C(CN)C(CN) CF₃ CH₃ H 4-Cl 1.307 C(CN) C(CN) CF₃ CH₃ H 2,4-Cl₂ 1.308 C(CN)C(CN) CF₃ CH₃ H 4-CF₃ 1.309 C(CN) C(CN) CF₃ CH₃ H 4-CN 1.310 C(CN) C(CN)CF₃ CH₃ H 4-phenoxy 1.311 C(CN) C(CN) CF₃ CH₃ CH₃ H 1.312 C(CN) C(CN)CF₃ CH₃ CH₃ 2-F 1.313 C(CN) C(CN) CF₃ CH₃ CH₃ 4-F 1.314 C(CN) C(CN) CF₃CH₃ CH₃ 2,4-F₂ 1.315 C(CN) C(CN) CF₃ CH₃ CH₃ 2-Cl 1.316 C(CN) C(CN) CF₃CH₃ CH₃ 4-Cl 1.317 C(CN) C(CN) CF₃ CH₃ CH₃ 2,4-Cl₂ 1.318 C(CN) C(CN) CF₃CH₃ CH₃ 4-CF₃ 1.319 C(CN) C(CN) CF₃ CH₃ CH₃ 4-CN 1.320 C(CN) C(CN) CF₃CH₃ CH₃ 4-phenoxy

BIOLOGICAL EXAMPLES

1. In-vivo test on Trichostrongylus colubriformis and Haemonchuscontortus on Mongolian gerbils (Meriones unquiculatus) UsingSubcutaneous Injection

Six to eight week old Mongolian gerbils are infected by artificialfeeding with ca. 2000 third instar larvae each of T. colubriformis andH. contortus. 6 days after infection, the gerbils are lightlyanaesthetised with N₂O and treated by subcutaneous injection into theneck area with the test compounds, dissolved in a mixture of 2 partsDMSO and 1 part polyethylene glycol 400, in quantities of 100, 32 and10-0.1 mg/kg. On day 9 (3 days after treatment), when most of the H.contortus that are still present are 4th instar larvae and most of theT. colubriformis are immature adults, the gerbils are killed in order tocount the worms. The efficacy is calculated as the % reduction of thenumber of worms in each gerbil, compared with the geometric average ofnumber of worms from 8 infected and untreated gerbils.

In this test, a vast reduction in nematode infestation is achieved withcompounds of formula I.

Totally analogous results are obtained upon oral administration of theactive ingredient.

2. Insecticidal Stomach Toxicant Activity on Spodoptera littoralis

Potted cotton plants at the 5-leaf stage are each sprayed with anacetonic/aqueous test solution containing 1, 3, 12.5 or 50 ppm of thecompound to be tested.

After drying of the spray deposit, the plants are colonised with ca. 30larvae (L₁ stage) of Spodoptera littoralis. Two plants are used per testcompound and per test species. The test is carried out at ca. 24° C. andat 60% relative humidity. Evaluations and intermediate evaluations onmoribund animals, larvae and feeding damage are made after 24, 48 and 72h.

The compounds of formula I achieve total mortality after 24 h at aconcentration of active ingredient of only 3 ppm.

3. Activity on Phytotoxic Acarids

OP-sensitive Tetranychus urticae

The primary leaves of bean plants (Phaseolus vulgaris) are covered 16hours before the test with a mass-cultivated piece of leaf infested withT. urticae. After removing the piece of leaf, the plants that areinfested with all stages of the mites are sprayed to drip point with atest solution containing either 0.2, 0.4 or 1.6 ppm of the compound tobe tested. The temperature in the greenhouse is ca. 25° C. After 7 days,an evaluation of the percentage of mobile stages (adults and nymphs) andof eggs is made under a microscope.

The compounds of formula I achieve total mortality at a concentration ofactive ingredient of 0.4 ppm.

4. Activity on L₁ Larvae of Lucilia sericata

1 ml of an aqueous suspension of the active substance to be tested isadmixed with 3 ml of a special larvae growth medium at ca. 50° C., sothat a homogenate of either 250 or 125 ppm of active ingredient contentis obtained. Ca. 30 Lucilia larvae (L₁) are used in each test tubesample. After 4 days, the mortality rate is determined. The compounds offormula I attain 100% activity with 250 ppm.

5. Acaricidal Activity on Boophilus microplus (Biarra Strain)

A piece of sticky tape is attached horizontally to a PVC sheet, so that10 fully engorged female ticks of Boophilus microplus (Biarra strain)can be adhered thereto by their backs, side by side, in a row. Using aninjection needle, 1 μl of a liquid is injected into each tick. Theliquid is a 1:1 mixture of polyethylene glycol and acetone and itcontains, dissolved therein, a certain amount of active ingredientchosen from 1, 0.1 or 0.01 μg per tick. Control animals are given aninjection without active ingredient. After treatment, the animals arekept under normal conditions in an insectarium at ca. 28° C. and at 80%relative humidity until oviposition takes place and the larvae havehatched from the eggs of the control animals. The activity of a testedsubstance is determined by IR₉₀, i.e. an evaluation is made of thedosage of active ingredient at which 9 out of 10 female ticks (=90%) layeggs that are infertile even after 30 days.

The compounds of formula I attain an IR₉₀ of 0.1 μg.

6. In vitro Efficacy on Engorged Female Boophilus microolus (BIARRA):

4×10 engorged female ticks of the OP-resistant BIARRA strain are adheredto a sticky strip and covered for 1 hour with a cotton wool ball soakedin an emulsion or suspension of the test compound in concentrations of500, 125, 31 and 8 ppm respectively. Evaluation takes place 28 dayslater based on mortality, oviposition and hatched larvae.

An indication of the activity of the test compounds is shown by thenumber of females that

die quickly before laying eggs,

survive for some time without laying eggs,

lay eggs in which no embryos are formed,

lay eggs in which embryos form, from which no larvae hatch, and

lay eggs in which embryos form, from which larvae normally hatch within26 to 27 days.

In this test, the compounds of formula I effect more than 80% rapidmortality of the female ticks.

7. Contact Action on Aphis craccivora

Pea seedlings that have been infested with all stages of development ofthe aphids are sprayed with a solution of active ingredient preparedfrom an emulsion concentrate, the solution containing 50, 25 or 12.5 ppmof active ingredient, as desired. After 3 days, an evaluation is made ofmore than 80% of aphids that are either dead or have fallen off. Only atthis level of activity is a preparation classified a s effective.

The compounds of formula I achieve total mortality (=100%) at aconcentration of 12.5 ppm.

8. Larvicidal Aactivity on Aedes aegypti

A sufficient quantity of a 0.1% acetonic solution of the activeingredient for a chosen concentration of 10, 3.3 or 1.6 ppm to beattained, is added by pipette to the surface of 150 ml of water in acontainer. After evaporation of the acetone, the container is coveredwith ca. 30-40 3-day old Aedes larvae. After 1, 2 and 5 days, themortality is tested.

In this test, the compounds of formula I at a concentration of 1.6 ppmeffect complete mortality of all larvae after only one day.

9. In vivo Efficacy on Adult Ctenocephalides felis on Domestic CatsAfter Oral Treatment

The test substances are given orally to domestic cats in a gelatincapsule before or after feeding, the dose varying between 0.5 and 20mg/kg. On days 1, 3, 7 and 10 after treatment, each cat is exposed to100 fleas (ca. 50 male and ca. 50 female), depending on the result ofprevious flea colonisation. The efficacy (in % reduction in fleanumbers) is based on the number of living fleas found after combing for10 minutes one day after each new flea colonisation, whereby theefficacy in % corresponds to the arithmetic average of the number ofliving fleas on control animals minus the number of living fleas on thetreated animals, divided by the arithmetic average of the number ofliving fleas on control animals and multiplied by 100.

The dying fleas found in the cat cages and by combing are collected,placed in an incubator at 28° C. and 70% relative humidity and after 24hours are tested for survival/mortality. If the majority of dying fleasdie, the test compound is regarded as a flea adulticide, and if themajority survive, the test compound shows “knock-down” activity.

In this test, the compounds of formula I effect at least 80% mortalityof the fleas.

10. In vivo Efficacy on Adult Ctenocephalides felis on Domestic CatsAfter Spot-on Treatment

The test substances are given to domestic cats as spot-on treatment, thedose varying between 0.5 and 10 mg/kg. On days 1, 3, 7 and 10 aftertreatment, each cat is exposed to 100 fleas (ca. 50 male and ca. 50female), depending on the result of previous flea colonisation.

The efficacy (in % reduction in flea numbers) is based on the number ofliving fleas found after combing for 10 minutes one day after each newflea colonisation, whereby the efficacy in % corresponds to thearithmetic average of the number of living fleas on control animalsminus the number of living fleas on the treated animals, divided by thearithmetic average of the number of living fleas on control animals andmultiplied by 100.

The dying fleas found in the cat cages and by combing are collected,placed in an incubator at 28° C. and 70% relative humidity and after 24hours are tested for survival/mortality. If the majority of dying fleasdie, the test compound is regarded as a flea adulticide, and if themajority survive, the test compound shows “knock-down” activity.

In this test, the compounds of formula I effect more than 90% mortalityof the fleas after 35 days.

11. In vitro Efficacy on Nymphs of Amblyomma hebraeum

About 5 fasting nymphs are placed in a polystyrene test tube containing2 ml of the test compound in solution, suspension or emulsion.

After immersion for 10 minutes, and shaking for 2×10 seconds on a vortexmixer, the test tubes are blocked up with a tight wad of cotton wool androtated. As soon as all the liquid has been soaked up by the cotton woolball, it is pushed half-way into the test tube which is still beingrotated, so that most of the liquid is squeezed out of the cotton-woolball and flows into a Petri dish below.

The test tubes are then kept at room temperature in a room with daylightuntil evaluated. After 14 days, the test tubes are immersed in a beakerof boiling water. If the ticks begin to move in reaction to the heat,the test substance is inactive at the tested concentration, otherwisethe ticks are regarded as dead and the test substances regarded asactive at the tested concentration. All substances are tested in aconcentration range of 0.1 to 100 ppm.

In this test, the compounds of formula I effect more than 80% mortalityof the ticks.

12. Activity Against Dermanyssus gallinae

2 to 3 ml of a solution containing 10 ppm active ingredient, and ca. 200mites (Dermanyssus gallinae) at different stages of development areadded to a glass container which is open at the top. Then the containeris closed with a wad of cotton wool, shaken for 10 minutes until themites are completely wet, and then inverted briefly so that theremaining test solution can be absorbed by the cotton wool. After 3days, the mortality of the mites is determined by counting the deadindividuals and indicated as a percentage.

The compounds of formula I show good activity against Dermanyssusgallinae.

13. Activity Against Musca domestica

A sugar cube is treated with a solution of the test substance in such away that the concentration of test substance in the sugar, after dryingover night, is 250 ppm. The cube treated in this way is placed on analuminium dish with wet cotton wool and 1.0 adult Musca domestica of anOP-resistant strain, covered with a beaker and incubated at 25° C. Themortality rate is determined after 24 hours.

In this test, the compounds of formula I show good activity againstMusca domestica.

What we claim is:
 1. A compound of formula

wherein R₁ is hydrogen, halogen, C₁-C₆-alkyl, C₁-C₆-alkoxy,C₁-C₆-haloalkyl or unsubstituted or mono- to penta-substituted phenyl,wherein the substituents are selected from the group consisting ofC₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, aryloxy, halogen, cyano andnitro, wherein the substituents may be identical or different; R₂ ishydrogen, C₁-C₆-alkyl, (C₁-C₆-alkylene)phenyl, pyridyl, COOR₆, CONR₇R₈,CORE, allyl or CH₂—O—R₆; R₃ is C₁-C₆-alkyl; R₄ is unsubstituted orsubstituted phenyl, unsubstituted or substituted benzyl or unsubstitutedor substituted heterocyclyl, whereby each of the substituents,independently of each other, is selected from the group consisting ofC₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, aryloxy, halogen, cyano,hydroxy, amino and nitro, wherein the substituents may be identical ordifferent; R₆ is C₁-C₆-alkyl, phenyl or benzyl; R₇ and R₈ independentlyof one another, are hydrogen or C₁-C₆-alkyl; Q is C₁-C₆-alkylene; X₁ isN or C(CN); X₂ is N, C(CN), C(COOR₆), C(COR₆), C(SOR₆), C(CONR₇R₈) orC(NO₂); X₃ and X₄, independently of each other, are O or S; and n is 0or
 1. 2. A process for preparing a compound of formula I according toclaim 1, comprising reacting a compound of formula

wherein R₁, R₂, X₁ and X₂ are defined as given for formula I with a) acompound of formula

wherein X₃, X₄, R₃, R₄, n and Q are defined as for formula I and Z is aleaving group, or b) a compound of formula

wherein X₄, R₄, n and Q are defined as for formula I, and Z is a leavinggroup and X₃ is O; introducing a nitroso group into the resultingproduct, producing an oxime; and reacting the oxime with a compound offormula R₃X₅  V, wherein X₃ is defined as for formula I and X₅ is aleaving group.
 3. A composition for controlling pests, which contains atleast one compound of formula I according to claim 1 as an activeingredient, in addition to carriers and/or dispersants.
 4. A method ofcontrolling pests, wherein a pesticidally active amount of at least onecompound of formula I according to claim 1 is used on the pests or on alocus thereof.
 5. A method for controlling pests according to claim 4,wherein the pests are parasites on a warm-blooded animal.
 6. A methodfor preparing a pharmaceutical composition against parasites, comprisingpreparing a compound of formula I of claim 1.